This proposal seeks to elucidate differences in susceptibility to large bowel neoplasms induced by 1,2-dimethylhydrazine (DMH) among various strains of mice. CF1 and SWR (DMH sensitive), AKR and DBA (DMH resistant) and C57 (moderately resistant) lines are being evaluated to determine if the acute proliferative response of colonic epithelial cells to DMH can be correlated with carcinogenicity. Three to four days after the first injection of the carcinogen, resistant strains show a compensitory overshoot or number of DNA synthesizing cells called up to reconstitute the mucosa equivalent with or slightly greater than that seen in the sensitive CF1 and SWR mice. This would indicate a similar degree of cytotoxicity of the carcinogen among the various strains. One week following the 6th injection of DMH, enlargement of the proliferative compartment occurred in all carcinogen treated mice although expansion was seen further up the crypt in the DMH sensitive strains. The CF1 and SWR strains also expressed markedly elevated labeling indices and increased mid crypt DNA synthesis at this time unlike the DMH resistant DBA and AKR animals. The proliferative parameters first reported in human mucosa and used to characterize the acute response of colonic epithelial cells to DMH appear to have great potential to describe differences in their degree of susceptibility to DMH although their specificity remains to be elucidated.